Function of the exoribonuclease pacman in cell movement and cell shape change

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Wound healing requires the surrounding skin cells to stretch, draw together and seal to cover the hole in the layer of skin cells. This process of wound healing is similar to other cell sheet movements in the development of all embryos. We have shown that an enzyme involved in the destruction of messenger RNAs is necessary for the cell sheet sealing process in the fruit fly Drosophila melanogaster. This enzyme, which is named Pacman, chews up these messenger RNAs from one end to the other. Messenger RNAs are the molecules which instruct the cell to make particular proteins. We have found out that Pacman is likely to be part of a large complex of proteins, a 'Death Star' which can efficiently destroy or imprison messenger RNAs. We suspect that Pacman must destroy RNAs that would potentially stop the cell sheet sealing process. The aim of this project is to find out how Pacman can control this hole closure process. The control mechanism probably involves targeting particular mRNAs for destruction by the 'Death Star' complex and we will test whether this is the case. Although this project will be carried out using the fruit fly Drosophila, it also has relevance for epithelial sheet sealing processes such as wound healing in humans as the cellular processes are surprisingly similar in both organisms. In addition, the Pacman enzyme is extremely similar between flies and humans therefore the insights we gain during this project may help us to improve the treatment for wounds and also help us to understand the cell movement process in embryos. The work described in this proposal is also directed towards the general question of gene regulation at the RNA level. It has recently become recognised that genes can be controlled at the level of the messenger RNA by using RNA itself as a tool to turn down specific genes. In a process termed RNA interference, it is possible to downregulate any particular RNA in the cell. Since Pacman and its homologues have been shown to be involved in RNA interference, this project will also may also provide innovative insights into the improval of this process for therapeutic purposes.